Adagen News

ADAGEN SUMMARY

ADAGEN ® (pegademase bovine) Injection is a modified enzyme used for enzyme replacement therapy for the treatment of severe combined immunodeficiency disease (SCID) associated with a deficiency of adenosine deaminase.

ADAGEN ® (pegademase bovine) Injection is indicated for enzyme replacement therapy for adenosine deaminase (ADA) deficiency in patients with severe combined immunodeficiency disease (SCID) who are not suitable candidates for - or who have failed - bone marrow transplantation. ADAGEN ® (pegademase bovine) Injection is recommended for use in infants from birth or in children of any age at the time of diagnosis. ADAGEN ® (pegademase bovine) Injection is not intended as a replacement for HLA identical bone marrow transplant therapy. ADAGEN ® (pegademase bovine) Injection is also not intended to replace continued close medical supervision and the initiation of appropriate diagnostic tests and therapy (e.g., antibiotics, nutrition, oxygen, gammaglobulin) as indicated for intercurrent illnesses.

Clinical Trials Related to Adagen (Pegademase)

EZN-2279 in Patients With ADA-SCID [Recruiting]
The purpose of this study is to evaluate the safety, efficacy, and pharmacokinetics of
EZN-2279 in patients with ADA-deficient combined immunodeficiency currently being treated
with Adagen.

Gene Transfer Therapy for Severe Combined Immunodeficieny Disease (SCID) Due to Adenosine Deaminase (ADA) Deficiency: A Natural History Study [Completed]
This study will monitor the long-term effects of gene therapy in patients with severe
combined immunodeficiency disease (SCID) due to a deficiency in an enzyme called adenosine
deaminase (ADA). It will also follow the course of disease in children who are not
receiving gene therapy, but may have received enzyme replacement therapy with the drug
PEG-ADA.
ADA is essential for the growth and proper functioning of infection-fighting white blood
cells called T and B lymphocytes. Patients who lack this enzyme are, therefore, immune
deficient and vulnerable to frequent infections. Injections of PEG-ADA may increase the
number of immune cells and reduce infections, but this enzyme replacement therapy is not a
definitive cure. In addition, patients may become resistant or allergic to the drug. Gene
therapy, in which a normal ADA gene is inserted into the patient's cells, attempts to
correcting the underlying cause of disease.
Patients with SCID due to ADA deficiency may be eligible for this study. Patients may or
may not have received enzyme replacement therapy or gene transfer therapy, or both.
Participants will have follow-up visits at the National Institutes of Health in Bethesda,
Maryland, at least once a year for a physical examination, blood tests, and possibly the
following additional procedures to evaluate immune function:

1. Bone marrow sampling - A small amount of marrow from the hip bone is drawn (aspirated)

through a needle. The procedure can be done under local anesthesia or light sedation.
2. Injection of small amounts of fluids into the arm to study if the patient's lymphocytes
respond normally.
3. Administration of vaccination shots.

4. Collection of white blood cells through apheresis - Whole blood is collected through a

needle placed in an arm vein. The blood circulates through a machine that separates it
into its components. The white cells are then removed, and the red cells, platelets
and plasma are returned to the body, either through the same needle used to draw the
blood or through a second needle placed in the other arm.
5. Blood drawings to obtain and study the patient's lymphocytes.

MND-ADA Transduction of CD34+ Cells From Children With ADA-SCID [Active, not recruiting]
Severe combined immune deficiency (SCID) may result from inherited deficiency of the enzyme
adenosine deaminase (ADA). Children with ADA-deficient SCID often die from infections in
infancy, unless treated with either a bone marrow transplant or with ongoing injections of
PEG-ADA (Adagen) enzyme replacement therapy. Successful BMT requires the availability of a
matched sibling donor for greatest success, and treatment using bone marrow from a less-well
matched donor may have a higher rate of complications. PEG-ADA may restore and sustain
immunity for many years, but is very expensive and requires injections 1-2 times per week on
an ongoing basis. This clinical trial is evaluating the efficacy and safety of an
alternative approach, by adding a normal copy of the human ADA gene into stem cells from the
bone marrow of patients with ADA-deficient SCID. Eligible patients with ADA-deficient SCID,
lacking a matched sibling donor, will be eligible if they meet entry criteria for adequate
organ function and absence of active infections and following the informed consent process.
Bone marrow will be collected from the back of the pelvis from the patients and processed in
the laboratory to isolate the stem cells and add the human ADA gene using a retroviral
vector. The patients will receive a moderate dosage of busulfan, a chemotherapy agent that
eliminates some of the bone marrow stem cells in the patient, to "make space" for the
gene-corrected stem cells to grow once they are given back by IV. Patients will be followed
for two years to assess the potentially beneficial effects of the procedure on the function
of their immune system and to assess possible side-effects. This gene transfer approach may
provide a better and safer alternative for treatment of patients with ADA-deficient SCID.

Treatment of SCID Due to ADA Deficiency With Autologous Transplantation of Cord Blood or Hematopoietic CD 34+ Cells After Addition of a Normal Human ADA cDNA by the EFS-ADA Lentiviral Vector [Completed]
This is a clinical gene transfer study that aims to verify the safety and efficacy of the
use of the EFS-ADA lentiviral vector to introduce the human adenosine deaminase (ADA) gene
into the hematopoietic progenitors of patients affected with severe combined
immunodeficiency due to ADA deficiency. The EFS-ADA vector expresses the human ADA cDNA
under the control of the elongation factor alpha short promoter (EFS). In addition, this
protocol will examine the effects of the ADA gene transfer on the immune system of treated
patients. Patients with ADA deficiency and ineligible for matched sibling allogeneic bone
marrow transplantation are eligible to participate in the study. To increase engraftment and
selected advantage or gene-corrected cells, busulfan will be used as a cytoreductive agent.
Enzyme replacement (PEG-ADA) will be discontinued 30 days after infusion of gene-corrected
cells. CD34+ hematopoietic progenitors will be isolated from the patient bone marrow,
peripheral blood or cord blood, exposed to lentiviral vector-mediated gene transfer and
re-infused into the patient through a peripheral vein. Clinical, immunological and molecular
follow-up studies will assess safety, toxicity, and efficacy of the procedure.

Gene Transfer Therapy for Severe Combined Immunodeficieny Disease (SCID) Due to Adenosine Deaminase (ADA) Deficiency [Completed]
This study will evaluate a new method for delivering gene transfer therapy to patients with
severe combined immunodeficiency disease (SCID) due to a defective adenosine deaminase (ADA)
gene. This gene codes for the adenosine deaminase enzyme, which is essential for the proper
growth and function of infection-fighting white blood cells called T and B lymphocytes.
Patients who lack this enzyme are vulnerable to frequent and severe infections.
Some patients with this disease receive enzyme replacement therapy with weekly injections of
the drug PEG-ADA (ADAGEN). This drug may increase the number of immune cells and reduce
infections, but it is not a cure. Gene transfer therapy, in which a normal ADA gene is
inserted into the patient s cells, attempts to correct the underlying cause of disease.
This therapy has been tried in a small number of patients with varying degrees of success.
In this study, the gene will be inserted into the patient s stem cells (cells produced by
the bone marrow that mature into the different blood components white cells, red cells and
platelets).
Patients with ADA deficiency and SCID who are taking PEG-ADA and are not candidates for
HLA-identical sibling donor bone marrow transplantation may be eligible for this study.
Participants will be admitted to the NIH Clinical Center for 2 to 3 days. Stem cells will
be collected either from cord blood (in newborn patients) or from the bone marrow. The bone
marrow procedure is done under light sedation or general anesthesia. It involves drawing a
small amount of marrow through a needle inserted into the hip bone. The stem cells in the
marrow will be grown in the laboratory and a normal human ADA gene will be transferred into
them through a special type of disabled mouse virus. A few days later, the patient will
receive the ADA-corrected cells through an infusion in the vein that will last from 10
minutes to 2 hours.
Patients will be evaluated periodically for immune function with blood tests, skin tests,
and reactions to tetanus, diphtheria, H. influenza B and S. pneumoniae vaccinations. The
survival of ADA-corrected cells will be monitored through blood tests. The number and
amount of blood tests will depend on the patient s age, weight and health, but is expected
that blood will not be drawn more than twice a month. Patients will also undergo bone
marrow biopsy aspirate (as described above) twice a year. Patients will be followed once a
year indefinitely to evaluate the long-term effects of therapy.